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Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence.


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Authors

Lisiecka, DM 
Holt, R 
Tait, R 
Ford, M 
Lai, M-C 

Abstract

During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development of white matter microstructure. This interaction may be present beyond the phenotype of autism in siblings of individuals with ASC, who are 10 to 20 times more likely to develop certain forms of ASC. We use diffusion tensor imaging to examine how white matter microstructure measurements correlate with age in typically developing individuals, and how this correlation differs in n=43 adolescents with ASC and their n=38 siblings. Correlations observed in n=40 typically developing individuals match developmental changes noted in previous longitudinal studies. In comparison, individuals with ASC display weaker negative correlation between age and mean diffusivity in a broad area centred in the right superior longitudinal fasciculus. These differences may be caused either by increased heterogeneity in ASC or by temporal alterations in the group's developmental pattern. Siblings of individuals with ASC also show diminished negative correlation between age and one component of mean diffusivity-second diffusion eigenvalue-in the right superior longitudinal fasciculus. As the observed differences match for location and correlation directionality in our comparison of typically developing individuals to those with ASC and their siblings, we propose that these alterations constitute a part of the endophenotype of autism.

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Keywords

Adolescent, Adolescent Development, Adult, Age Factors, Autistic Disorder, Child, Diffusion Tensor Imaging, Endophenotypes, Female, Humans, Male, Phenotype, Siblings, White Matter, Young Adult

Journal Title

Transl Psychiatry

Conference Name

Journal ISSN

2158-3188
2158-3188

Volume Title

5

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (G0701919)
Medical Research Council (G0001354)
Medical Research Council (G1000183)
This research was funded by an MRC Clinician Scientist Fellowship to MDS from the UK Medical Research Council (G0701919). LRC was supported by the Gates Cambridge Scholarship Trust. SB-C was supported by the Wellcome Trust, the MRC and the Autism Research Trust, during the period of this work.